Change In Defibrillation Threshold Research Articles

Predictive modeling of defibrillation using hexahedral and tetrahedral finite element models: recent advances

Implanted cardioverter/defribillator (ICD) implants may be complicated by body size and anatomy. One approach to this problem has been the adoption of creative, extracardiac implant strategies using standard ICD components. Because data on safety or efficacy of such ad hoc implant strategies are lacking, we have developed image-based finite element models to compare electric fields and expected defibrillation thresholds (DFTs) using standard and novel electrode locations. In this article, we review recently published studies by our group using such models and progress in meshing strategies to improve efficiency and visualization. Our preliminary observations predict that they may be large changes in defibrillation thresholds with clinically relevant variations of electrode placement. Extracardiac ICDs of various lead configurations are predicted to be effective in both children and adults. This approach may aid both ICD development and patient-specific optimization of electrode placement, but the simplified nature of current models dictates further development and validation before clinical or industrial use.

A novel ultrasound technique to estimate right ventricular geometry during fibrillation

Finite element modelling of the heart for the purpose of studying the electric fields of defibrillation shocks requires knowledge of the geometry of the heart during fibrillation. However, the standard method of measuring this geometry, MRI, cannot be used during fibrillation because the heart geometry changes rapidly and perhaps unpredictably. We present a new ultrasound approach to measuring the right ventricular geometry during fibrillation and preliminary data using this technique. In six anaesthetized pigs, we find that a short axis cross-sectional area of the right ventricle increases by 38% during a 30 s episode of ventricular fibrillation. A long axis cross-sectional area increases by 19% during this same time. By fitting parameters of a simple geometric model to the experimental data, we estimate that the volume of blood in the right ventricular cavity increases by approximately 30% during the episode of ventricular fibrillation. We present the first study of the RV area during fibrillation with the estimated volume. Our data suggest changes in defibrillation threshold may be linked to current shunting through the increased blood volume.

Temporal decline in defibrillation thresholds with an active pectoral lead system

OBJECTIVESThe objective of this study was to characterize temporal changes in defibrillation thresholds (DFTs) after implantation with an active pectoral, dual-coil transvenous lead system.BACKGROUNDVentricular DFTs rise over time when monophasic waveforms are used with non-thoracotomy lead systems. This effect is attenuated when biphasic waveforms are used with transvenous lead systems; however, significant increases in DFT still occur in a minority of patients. The long-term stability of DFTs with contemporary active pectoral lead systems is unknown.METHODSThis study was a prospective assessment of temporal changes in DFT using a uniform testing algorithm, shock polarity and dual-coil active pectoral lead system. Thresholds were measured at implantation, before discharge and at long-term follow-up (70 ± 40 weeks) in 50 patients.RESULTSThe DFTs were 9.2 ± 5.4 J at implantation, 8.3 ± 5.8 J before discharge and 6.9 ± 3.6 J at long-term follow-up (p < 0.01 by analysis of variance; p < 0.05 for long-term follow-up vs. at implantation or before discharge). The effect was most marked in a prespecified subgroup with high implant DFTs (≥15 J). No patient developed an inadequate safety margin (<9 J) during follow-up.CONCLUSIONSThe DFTs declined significantly after implantation with an active pectoral, dual-coil transvenous lead system, and no clinically significant increases in DFT were observed. Therefore, routine defibrillation testing may not be required during the first two years after implantation with this lead system, in the absence of a change in the cardiac substrate or treatment with antiarrhythmic drugs.

Pinacidil's Effects on Defibrillation Outcomes: Role of Increased Potassium Conductance Via the K(ATP) Channel.

BACKGROUND: It has been shown that the inhibition of potassium ion conductance decreases defibrillation threshold. We postulated that if potassium conductance is a primary mechanism affecting defibrillation threshold values, then increasing potassium ion conductance will increase defibrillation values. The primary objective of this study was to determine if the ATP-dependent potassium (K(ATP)) channel opener pinacidil would increase defibrillation threshold values. The second objective was to prove that the observed changes were due to potassium conductance by using the K(ATP) inhibitor, glyburide, to reverse the electrophysiologic actions of pinacidil. The third objective was to determine if the electrophysiology action sof pinacidil correlate with changes in defibrillation threshold value. METHODS AND RESULTS: Domestic farm swine (n = 14) were anesthetized and intubated. Subsequently, they were instrumented with monophasic action potential catheters and epicardial defibrillation patches. Defibrillation threshold values, action potential duration, effective refractory period, and ventricular fibrillation cycle length were determined at baseline and during treatment phase 1 and treatment phase 2. Pigs were randomized into 2 groups: group 1 (n = 6) received D(5)W in treatment phase one followed by D(5)W in treatment phase 2 and group 2 (n = 8) received pinacidil in treatment phase one followed by the addition of glyburide in treatment phase two. DFT(ED50) did not change at baseline, treatment phase one or treatment phase two for group 1 (10.5 +/- 2, 11.1 +/- 1.7, 10.5 +/- 1.0 J) or for group 2 (10.1 +/- 2.2, 11.4 +/- 4.2, 11.4 +/- 3.0 J). Electrophysiologic parameters )QRS, effective refractory period, action potential duration(90), and ventricular fibrillation cycle length) were not significantly changed from baseline in group 1. In contrast, effective refractory period, action potential duration(90), and ventricular fibrillation cycle length significantly decreased at all recorded sites after the administration of pinacidil in group 2 (range of 7-13%, 6-9%, and 12-17%, respectively). However, pinacidil did not change the basal level of dispersion in effective refractory period, action potential duration, and ventricular fibrillation cycle length during paced rhythm or ventricular fibrillation. Glyburide reversed pinacidil's electrophysiologic actions. CONCLUSIONS: Pinacidil does not alter defibrillation threshold, but it reduces effective refractory period, action potential duration, and ventricular fibrillation cycle length and does not increase electrical heterogeneity. Therefore, changes in potassium channel conductance as well as shortening repolarization are unlikely primary mechanisms for elevating defibrillation threshold.

Mechanisms of antiarrhythmic drug-induced changes in defibrillation threshold: Role of potassium and sodium channel conductance

Objectives.We sought to determine which ion current predominantly affects defibrillation outcomes by using specific pharmacologic probes (lidocaine [a sodium channel blocking agent] and cesium [an outward potassium channel blocking agent]) in 26 swine.Background.The effect of a drug on sodium or potassium channel conductance, or both, may affect defibrillation threshold values. However, it is unknown which ion channel predominates.Methods.Each pig was randomly assigned to one of four treatment groups with two treatment phases: groupI = placebo (D5W) in treatment phase I followed by placebo plus cesium in treatment phase II (n = 6); group 2= lidocaine followed by lidocaine plus placebo (n = 7); group 3= lidocaine followed by lidocaine plus cesium (n = 7); group 4= placebo followed by placebo plus placebo (n = 6). Defibrillation threshold values and electrocardiographic measurements were obtained at baseline and at treatment phases I and II.Results.Lidocaine increased defibrillation threshold values from baseline by 71% in group 2 (p = 0.02) and by 92% in group 3 (p < 0.01). There were no changes in defibrillation threshold values from baseline to D5W in groups 1 and 4. When D5W was added to lidocaine in group 2 and D5W in group 4, there were no significant changes in defibrillation threshold values. However, when cesium was added to lidocaine in group 3, the elevated defibrillation threshold values (mean ± SD) returned to baseline values (from 15.7 ± 3.46 to 7.55 ± 3.19 J, p < 0.01). Cesium added to D5W in group 1 also significantly reduced defibrillation threshold values from 7.10 ± 1.27 to 4.14 ± 1.75 J (p < 0.01). The effect of cesium on defibrillation threshold values was similar between groups 1 and 3, regardless of lidocaine, such that these values were reduced by 40 ± 14% and 51 ± 18%, respectively (p = 0.28).Conclusions.Cesium, through potassium blockade, reverses lidocaine-induced elevation in defibrillation threshold values. The magnitude of defibrillation threshold reduction when cesium was added to lidocaine was similar to the defibrillation threshold reduction when cesium was added to placebo. Thus, inhibiting outward potassium conductance and prolonging repolarization decreases defibrillation threshold values independent of sodium channel blockade.

Early Changes in Defibrillation Threshold Following Implantation of a Nonthoracotomy System in Dogs

Nonthoracotomy systems are rapidly becoming the preferred surgical method for implantation of cardioverter defibrillators. Testing is performed at the time of implantation to insure an adequate margin of safety for defibrillation. However, this safety margin may change with lead maturation. This study evaluated changes in defibrillation threshold following implantation of a nonthoracotomy system. Ten dogs underwent implantation of a nonthoracotomy system consisting of a single catheter with a distal coil electrode in the right ventricular apex and a proximal coil electrode in the superior vena cava forming a common anode with a subcutaneous patch over the left thorax. Defibrillation threshold testing, using a biphasic waveform, was performed on each animal under general anesthesia at implantation (day 1) and subsequently on postoperative days 3, 7, 10, 17, 24, 31, 38, and 45. E50, the energy associated with a 50% likelihood of successful defibrillation, was determined at each setting. The mean E50 was 12.2 +/- 1.1 J at the time of implantation, increasing 36% to 16.8 +/- 2.0 J by day 38 (P < 0.01). Individual increases in E50 of 10-12 J were observed in four animals. Energy requirements for defibrillation with a nonthoracotomy system increase during the early postoperative period, with the highest defibrillation threshold observed at 38 days. This increase may be applicable to humans and should be considered when selecting an adequate energy safety margin for defibrillation at time of implantation.

The Effect of Chronic Oral and Acute Intravenous Amiodarone Administration on Ventricular Defibrillation Threshold Using Implanted Electrodes in Dogs

The effect of acute intravenous administration and chronic oral loading of amiodarone on defibrillation threshold was evaluated in normal anesthetized dogs using implanted superior vena caval spring and left ventricular patch electrodes. The effect of oral loading with amiodarone was evaluated by comparing three groups of six dogs each that received either no drug, 200 mg/day for 9 days, or 400 mg/day for 9 days. Defibrillation threshold was evaluated by administering a fixed sequence of shocks with increasing energies until defibrillation was successful. Defibrillation was determined 13 times in each animal. The mean defibrillation threshold (plus or minus standard error of the mean) was 7.5 +/- 0.3 J in the control group, 15.4 +/- 0.6 J in the group receiving amiodarone 200 mg/day, and 17.9 +/- 0.8 J for the group receiving 400 mg/day. These values are significantly different using analysis of variance and Tukey's test. The acute effect of intravenous amiodarone, 5 mg/Kg was evaluated in five dogs using each dog as its own control. The mean defibrillation threshold during control period was 10.8 +/- 0.4 J, and during the first two hours after amiodarone administration was 10.8 +/- 0.4 J. There was no significant difference. Thus, in this study oral administration of a loading dose of amiodarone comparable to that used in patients produced a dose dependent increase in defibrillation threshold, whereas no change in defibrillation threshold was observed acutely after intravenous administration.

Adrenergic effects on internal cardiac defibrillation threshold.

Autonomic neural tone modulates arrhythmias and could affect the efficacy of an implantable defibrillator if defibrillation threshold is also altered by changes in neural activity. We determined the effects of alpha- and beta-adrenoceptor agonists and antagonists on the energy requirement for defibrillation using a sequential-pulse technique in anesthetized pigs. The doses for each drug were selected based on the results of dose-response curves. The mean defibrillation threshold was 10.2 +/- 0.65 J (mean +/- SE) in control and 10.0 +/- 0.84, 9.4 +/- 0.87 and 8.9 +/- 0.89 J during phenylephrine infusions of 0.7, 1.35, and 2.0-4.0 micrograms X kg-1 X min-1 [n = 8, P = not significant (NS)]. Phenylephrine at all infusion rates increased the ventricular fibrillation threshold, indicating that effects on the ventricular fibrillation threshold may occur independent of changes in defibrillation threshold. No significant change was observed in the defibrillation threshold before and after administration of isoproterenol (6.5 +/- 0.72 and 6.7 +/- 0.93 J, n = 8, P = NS). Similarly, no change in defibrillation thresholds was observed after 1.5-2.0 mg/kg phentolamine (8.5 +/- 0.85 and 7.9 +/- 0.93 J, n = 8, P = NS) or 3.0-6.0 mg/kg atenolol (10.0 +/- 1.7 and 10.3 +/- 2.6 J, n = 8, P = NS). However, when defibrillation threshold was determined using a single-pulse method, isoproterenol infusion produced a significant decrease (17.3 +/- 1.5 vs. 14.6 +/- 1.9 J, n = 7, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Beta-adrenergic modulation of direct defibrillation energy in anesthetized dog heart.

Catecholamines facilitate ventricular defibrillation in animals. We examined the effects of beta-adrenergic stimulation and blockade on ventricular defibrillation threshold in anesthetized dogs. Calibrated shocks were delivered between epicardial and superior vena caval electrodes, and defibrillation threshold was measured before and after administration of isoproterenol and propranolol. Eight dogs (group 1) received isoproterenol before propranolol. Nine dogs (group 2) received propranolol before isoproterenol. In group 1, the minimum energy required to defibrillate before isoproterenol was 10.6 +/- 1.7 (SE) J and decreased to 5.9 +/- 1.3 with isoproterenol (P less than 0.001). In group 2, the minimum energy required to defibrillate was 8.3 +/- 2.4 J before propranolol and increased to 10.7 +/- 2.2 after propranolol (P less than 0.001). In group 1, propranolol after isoproterenol increased defibrillation threshold (P less than 0.07), whereas in group 2 isoproterenol after propranolol produced no significant change in defibrillation threshold. Thus beta-stimulation decreased defibrillation threshold significantly in the anesthetized dog heart, an effect that was blocked by propranolol. Conversely, propranolol increased defibrillation threshold, an effect that occurred despite prior beta-stimulation, probably because of the short half-life of isoproterenol.

The effect of newer antiarrhythmic drugs on defibrillation threshold

This study was conducted to determine the effects of clofilium phosphate and bretylium tosylate on ventricular defibrillation threshold. Dogs were anesthetized with pentobarbital and subjected to repeated fibrillation-defibrillation episodes. Defibrillation thresholds were determined at 15-min intervals, using underdamped 5--6 msec sinusoidal current shocks, from 30 min before drug injection to 120 min after injection. Eight dogs were given clofilium phosphate (0.34 mg/kg, iv). Another 10 dogs were given bretylium tosylate (10.0 mg/kg, iv). Both drugs lowered defibrillation threshold from 15--90 min after injection. The maximum clofilium effect was a 31% decrease in threshold current and a 54% decrease in threshold energy. The greatest decrease in defibrillation threshold produced by bretylium was 16% for current and 31% for energy. These drug induced changes in defibrillation threshold are of potential clinical benefit if they occur in human subjects at doses which are effective for control of ventricular arrhythmias.

Dependence of defibrillation threshold upon extracellular/intracellular K + concentrations

The effect of increasing extracellular potassium concentration (Ko) upon electrical ventricular defibrillation threshold was investigated in pentobarbital anesthetized dogs treated with intravenous potassium chloride. Defibrillation threshold fell duirng potassium intoxication. The percent decrease in defibrillation threshold was linearly related to the logarithm of Ko and to the potassium equilibrium potential (Ek), calculated from measured extracellular and intracellular potassium concentrations of ventricular muscle. In dogs supported by left ventricular bypass in order to maintain the circulation during potassium intoxication, the values of Ko and Ek required for spontaneous, K+ induced defibrillation (electrical defibrillation threshold = zero) were 16.6 mEq/L and -46 mV compared to the normal values of 3.9 mEq/L and -84 mV. Changes in defibrillation threshold related to changes in Ek may be significant events in digitalis intoxication and in myocardial anoxia during prolonged fibrillation.